Centre for Neuroscience, 513 HMRC, University of Alberta, Edmonton, AB, T6G 2S2, Canada.
Neurosci Biobehav Rev. 2011 May;35(6):1419-49. doi: 10.1016/j.neubiorev.2011.03.005. Epub 2011 Mar 21.
The brain's serotonin (5-HT) system is key in the regulation of reward-related behaviours, from eating and drinking to sexual activity. The complexity of studying this system is due, in part, to the fact that 5-HT acts at many receptor subtypes throughout the brain. The recent development of drugs with greater selectivity for individual receptor subtypes has allowed for rapid advancements in our understanding of this system. Use of these drugs in combination with animal models entailing selective reward measures (i.e. intracranial self-stimulation, drug self-administration, conditioned place preference) have resulted in a greater understanding of the pharmacology of reward-related processing and behaviour (particularly regarding drugs of abuse). The putative roles of each 5-HT receptor subtype in the pharmacology of reward are outlined and discussed here. It is concluded that the actions of 5-HT in reward are receptor subtype-dependent (and thus should not be generalized) and that all studied subtypes appear to have a unique profile which is determined by content (e.g. receptor function, localization - both throughout the brain and within the synapse) and context (e.g. type of behavioural paradigm, type of drug). Given evidence of altered reward-related processing and serotonergic function in numerous neuropsychiatric disorders, such as depression, schizophrenia, and addiction, a clearer understanding of the role of 5-HT receptor subtypes in this context may lead to improved drug development and therapeutic approaches.
大脑中的血清素(5-HT)系统在调节与奖励相关的行为方面起着关键作用,包括饮食、性行为等。研究该系统的复杂性部分源于 5-HT 在大脑中的许多受体亚型中发挥作用。最近开发出了对个别受体亚型具有更高选择性的药物,这使得我们对该系统的理解取得了快速进展。这些药物与涉及选择性奖励措施的动物模型(例如颅内自我刺激、药物自我给药、条件性位置偏好)一起使用,使得我们对与奖励相关的加工和行为的药理学(特别是关于滥用药物)有了更深入的了解。本文概述和讨论了每个 5-HT 受体亚型在奖励药理学中的作用。结论认为,5-HT 在奖励中的作用取决于受体亚型(因此不应一概而论),并且所有研究的亚型似乎都具有独特的特征,这些特征由内容(例如受体功能、定位-既在整个大脑中,也在突触内)和背景(例如行为范式的类型、药物的类型)决定。鉴于在许多神经精神疾病(如抑郁症、精神分裂症和成瘾)中都存在与奖励相关的处理和血清素能功能改变的证据,因此,更清楚地了解 5-HT 受体亚型在这方面的作用可能会导致更好的药物开发和治疗方法。